Organismal biology (OrgBio) comprises the diversity, structures, and functions of all organisms from bacteria to humans. Arguably, OrgBio is often the most poorly taught and least conceptually rigorous section of the introductory biology sequence offered at most U.S. institutions of higher education. This article reports on the successful implementation of conceptual and pedagogical reforms in an introductory OrgBio course offered at a large public university. Conceptual reforms were based on a theoretical framework consisting of universal physical and chemical laws, deep molecular homologies, and diverse structure-function relationships. Pedagogical reforms involved the development of group active engagements (GAEs) that were designed to encourage students to develop their abilities to engage in principles-based reasoning. A new model for characterizing different approaches toward principles-based reasoning in biology was developed to analyze these GAEs. Two surveys indicated that OrgBio students developed more favorable perceptions about the effectiveness of GAE-based course offerings, as compared to similar lecture-based versions.